South Asians (individuals from India, Pakistan, Nepal, Bangladesh, and Sri Lanka) represent a quarter of the world's population and are one of the fasting growing ethnic groups in the United States. Several cross-sectional studies conducted worldwide have reported a high prevalence of atherosclerosis, diabetes, hypertension, and cardiovascular disease in this ethnic group, despite low body mass index. However, there are no longitudinal studies of South Asians to determine other risk factors that may explain the high prevalence of cardiovascular disease. We performed a pilot community-based cross-sectional study of South Asian men and women in the San Francisco Bay Area. We collaborated with investigators involved with the Multi-Ethnic Study of Atherosclerosis (MESA), an NHLBI-supported prospective cohort study of four U.S. ethnic groups (Whites, African Americans, Latinos, and Chinese Americans). We used identical methods and measures for data collection to efficiently compare the South Asian sample with the MESA ethnic groups. We found that South Asians had higher socioeconomic attainment, lower smoking and alcohol use, relatively low BMI and waist circumference, and higher hypertension and diabetes prevalence. Common carotid intima media thickness was significantly higher in the South Asians compared to all ethnic groups in MESA, but coronary artery calcium scores were similar to all other ethnic groups. We now propose a prospective cohort study of 900 South Asian individuals to determine other risk factors linked to atherosclerosis and disease progression. We will conduct a two-center prospective cohort study of 900 South Asian adults between the ages of 40 and 79 years without cardiovascular disease from the San Francisco Bay Area and Chicago area to determine etiologic associations and prognostic significance of subclinical atherosclerosis and to compare these findings with other U.S. ethnic groups in MESA. Our specific aims are to determine whether (1) traditional, social/cultural/behavioral and novel risk factors are associated with subclinical atherosclerosis measures;(2) South Asians have higher prevalence of subclinical atherosclerosis than the four ethnic groups in the MESA 5th examination after adjusting for traditional, social/behavioral, and novel risk factors. In an exploratory aim, we will determine whether measures of subclinical atherosclerosis are associated with incident cardiovascular events after 2 years of follow-up. Understanding the antecedents of atherosclerosis in this high-risk ethnic population may lend insight into the pathogenesis of cardiovascular disease in general. The identification of key risk factors that are linked to atherosclerosis will provide targets for future therapies to prevent or cure the leading cause of death worldwide - cardiovascular disease. PUBLIC HEALTH RELEVANCE: South Asian (Indian, Pakistani, Bangladeshi, Nepali, and Sri Lankan) individuals have high rates of cardiovascular disease that is not explained by traditional cardiovascular risk factors. Though South Asians represent over one-quarter of the world's population, there are no longitudinal studies in this high-risk ethnic group. We aim to establish a longitudinal study of South Asians at two U.S. centers to identify risk factors linked to subclinical atherosclerosis and incident cardiovascular disease. These will provide targets for future therapies to prevent or cure the leading cause of death worldwide, cardiovascular disease.